Yttrium-90-labeled monoclonal antibody for therapy: labeling by a new macrocyclic bifunctional chelating agent

S. V. Deshpande, S. J. DeNardo, D. L. Kukis, M. K. Moi, M. J. McCall, Gerald L Denardo, C. F. Meares

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170 Scopus citations

Abstract

Yttrium-90 (90Y) is a promising radiometal for therapy of cancer due to its high-energy beta emission and a physical half-life of 2.67 days. Bifunctional chelating agents based on DTPA cyclic anhydride or EDTA do not form Y(III) complexes that are stable under physiologic conditions. A new macrocyclic bifunctional chelating agent based on 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) forms a stable Y(III) complex. It was converted to p-bromoacetamidobenzyl-DOTA (BAD), and conjugated to monoclonal antibody Lym-1 via 2-iminothiolane, either as the free ligand or as the 88Y chelate. Stability studies of Lym-1-2IT-BAD-88Y in human serum in vitro showed no measurable loss of Y(III) from the ligand over a 25-day period. In Raji-tumored mice, tumor uptake was 16.8% of the injected dose per gram of tissue on Day 3. The bone uptake was 2.0, 3.6, and 2.1% injected dose per gram of tissue on Day 1, 3, and 5, respectively. The biodistribution of the control 88Y-citrate demonstrated continuous increase in bone uptake from 13.8% injected dose per gram on Day 1 to 24.9% injected dose per gram on Day 4.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalJournal of Nuclear Medicine
Volume31
Issue number4
StatePublished - 1990

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

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    Deshpande, S. V., DeNardo, S. J., Kukis, D. L., Moi, M. K., McCall, M. J., Denardo, G. L., & Meares, C. F. (1990). Yttrium-90-labeled monoclonal antibody for therapy: labeling by a new macrocyclic bifunctional chelating agent. Journal of Nuclear Medicine, 31(4), 473-479.